There are many fields in which systems are subject to progressive, or gradually changing (usually increasing), dysfunction. In the medical or veterinary field, for example, the human or animal body, or more particularly certain parts of it, may be subject to gradual deterioration as a result of disease or aging. Non-biological systems, such as mechanical, electrical or electronic systems, are also usually subject to gradual deterioration, again through aging or wear or the gradually changing (usually increasing) accumulation of faults. It is desirable to be able to monitor and quantify such progressive dysfunction. However, it can be difficult to do this in a consistent and quantitative way. This is particularly true in the case of multilateral dysfunction, i.e. dysfunction which arises in several different parts of the system. Techniques are available for detecting such multilateral dysfunction, but the consistent and quantitative characterisation of such dysfunction is problematic.
A medical example can be used to demonstrate the problems. Parkinson's disease is a disorder of the central nervous system that affects between one and one-and-a-half million U.S. citizens. Parkinson's disease can appear at any age, but it is uncommon in people younger than 30, and the risk of developing it increases with age. It occurs in all parts of the world, and men are affected slightly more often than women. Patients with the disease suffer severe motor-neuro symptoms, including shaking, rigidity, slowness of movement and poor balance.
The progression of Parkinson's disease can be monitored by nuclear medical imaging of the two striata of the brain (left and right). A characteristic of Parkinson's disease is the lack of dopamine in the striatum of the brain, caused by the loss of neurons in the substantia nigra. The amount of dopamine in the striatum can be measured by injecting a radioligand (for example ioflupane (FP-CIT/DaTSCAN) or iodobenzamide (IBZM)); after the radioactive labeled molecules arrive at the dopaminergic terminals in the striatum, they bind to pre-synaptic dopamine transporters molecules which enables imaging of functional dopaminergic neurons using Single Photon Emission Computed Tomography (SPECT).
The SPECT image of a normal person shows high uptake in the left and right striatum, as shown in FIGS. 1(a) and (b) of the accompanying drawings. These images are SPECT images with 123I tracer (here DaTSCAN) showing the striatum as “hotspots”. FIG. 1(a) is a close-up of one of the striata in FIG. 1(b). In the case of Parkinson's disease, the number of dopamine transporters in the striatum is substantially reduced. The SPECT image of a typical Parkinson's disease patient shows reduced uptake in the striatum, and in some patients there is asymmetry in the level of uptake between the left and right striatum. Such an image is shown in FIG. 1(c) of the accompanying drawings.
FIGS. 2(a), (b) and (c) show typical disease progression for a single striatum. As the disease progresses, the tail of the striatum, the putamen, dies off first, followed finally by the upper region, the caudate. FIG. 2(a) shows a healthy striatum, progressing in FIG. 2(b) to a moderately degenerated one where the putamen tail has very reduced uptake, and finally in FIG. 2(c) an extremely degenerated striatum with little uptake at all in either putamen or caudate.
Existing techniques for analysing these SPECT images involve independent measures of the amount of uptake in the left and right striata, with a possible additional calculation to indicate the degree of asymmetry. For example, one way of measuring the degree of dysfunction has been proposed in which a standard fixed-size rectangle is placed over each striatum in the image, and uptake in each rectangle computed by summing intensities. Uptake ratios are computed for the left and right striatum, and a measure of asymmetry is produced.
A. Lokkegaard, L. M. Werdelin and L. Friberg proposed a similar technique in “Clinical Impact of Diagnostic SPECT Investigations with a Dopamine Re-Uptake Ligand”, European J. Nuclear Medicine, Vol. 29, No. 12, December 2002. In this proposal a standard fixed-size shape is used to divide the striatum into two parts, the caudate and putamen. Uptake in each part is computed separately by summing intensities of pixels within each region. These quantities are then used to compute uptake ratios.
However in both of these techniques it is difficult to relate the result to the state of progression of the disease and it is difficult to know what level of confidence there is in the result. Furthermore, the summing of intensities over the whole or a large part of the striatum, while a deliberate simplification, loses the information in the distribution of the uptake across the striatum.
Similar bilateral or multilateral dysfunctions occur in other medical conditions such as osteoarthritis in the knees, lung performance (for example in smoker's lungs) or the build-up of neurocapillary tangles in the brain of Alzheimer's disease sufferers. Similarly, multilateral system dysfunction occurs in non-biological systems, such as complex machines, or collections of machines, for example in a factory setting. Thus techniques allowing better characterisation of such progressive multilateral dysfunction, for example in better indicating the degree of progression of the dysfunction and in giving an indication of confidence in the measurement, would be useful.